Higher blood pressure in adolescent boys after very preterm birth and fetal growth restriction

Abstract

Background: Although preterm birth predisposes for cardiovascular disease, recent studies in children indicate normal blood pressure and arterial stiffness. This prospective cohort study therefore assessed blood pressure and arterial stiffness in adolescents born very preterm due to verified fetal growth restriction (FGR).

Methods: Adolescents (14 (13-17) years; 52% girls) born very preterm with FGR (preterm FGR; n = 24) and two control groups born with appropriate birth weight (AGA), one in similar gestation (preterm AGA; n = 27) and one at term (term AGA; n = 28) were included. 24-hour ambulatory blood pressure and aortic pulse wave velocity (PWV) and distensibility by magnetic resonance imaging were acquired.

Results: There were no group differences in prevalence of hypertension or in arterial stiffness (all p ≥ 0.1). In boys, diastolic and mean arterial blood pressures increased from term AGA to preterm AGA to preterm FGR with higher daytime and 24-hour mean arterial blood pressures in the preterm FGR as compared to the term AGA group. In girls, no group differences were observed (all p ≥ 0.1).

Conclusions: Very preterm birth due to FGR is associated with higher, yet normal blood pressure in adolescent boys, suggesting an existing but limited impact of very preterm birth on cardiovascular risk in adolescence, enhanced by male sex and FGR.

Impact: Very preterm birth due to fetal growth restriction was associated with higher, yet normal blood pressure in adolescent boys. In adolescence, very preterm birth due to fetal growth restriction was not associated with increased thoracic aortic stiffness. In adolescence, very preterm birth in itself showed an existing but limited effect on blood pressure and thoracic aortic stiffness. Male sex and fetal growth restriction enhanced the effect of preterm birth on blood pressure in adolescence. Male sex and fetal growth restriction should be considered as additional risk factors to that of preterm birth in cardiovascular risk stratification.

Fig. 1. Inclusion flowchart.

Upper panel shows initial inclusion of the original cohort. Middle panel shows the current follow-up in adolescence. Lower panel shows the number of individuals who underwent 24-hour ABPM and MRI. FGR fetal growth restriction, AGA appropriate for gestational age, MRI magnetic resonance imaging, 24-hour ABPM 24-hour ambulatory blood pressure measurements.

Fig. 2. Measurement of pulse wave velocity in the thoracic aorta.

a Shows non-contrast-enhanced 3D angiography of the thoracic aorta with flow measurement planes (solid lines) perpendicular to the ascending aorta and descending aorta at diaphragm level, and the aortic centerline distance (Δd; dashed line) between flow measurement planes. b Shows delineations of the ascending aorta in a magnitude image (b1) and phase-contrast image (b2). c Shows corresponding delineations of the descending aorta at diaphragm level (c1 and c2). d Shows flow curves for the ascending aorta (solid line) and descending aorta (dashed line) used to assess pulse wave velocity using the time-to-foot method. Pulse wave traveling time (Δt) was calculated as the time between upslope tangents intersecting the baseline. Pulse wave velocity was calculated by dividing the aortic centerline distance (Δd) with the time difference (Δt).

Fig. 3. 24-hour ambulatory blood pressure measurements in boys (left panel) and girls (right panel).

Upper row shows systolic blood pressures, middle row shows diastolic blood pressures and lower row shows mean arterial blood pressure. Left panel shows daytime blood pressures, middle panel show nighttime blood pressures and right panel shows 24-hour blood pressures in adolescents born preterm with fetal growth restriction (preterm FGR), preterm with birth weight appropriate for gestational age (preterm AGA), and adolescents born at term (term AGA). For boys, median daytime and 24-hour mean arterial blood pressures were higher in preterm FGR compared to the term AGA group ((93 (88–101 mmHg) vs. 86 (76–101 mmHg); p = 0.03) and (88 (85–97 mmHg) vs. 82 (73–93 mmHg); p = 0.03, respectively)). FGR fetal growth restriction, AGA birth weight appropriate for gestational age. Lines indicate median.

Fig. 4. Thoracic aortic pulse wave velocity and aortic distensibility.

Left graph shows pulse wave velocity, middle graph shows distensibility in the ascending aorta and right graph shows distensibility in the descending aorta at diaphragm level. Closed circles indicate boys and open circles indicate girls. For girls, median pulse wave velocity was higher in preterm AGA group as compared to the term AGA group (3.9 m/s vs. 3.5 m/s; p = 0.04). FGR fetal growth restriction, AGA birth weight appropriate for gestational age. Lines indicate median.